Using Next-generation Sequencing to Identify Novel Exosomal miRNAs as Biomarkers for Significant Hepatic Fibrosis.

OBJECTIVE

The aim of this study is to determine the role of serum exosomal miRNAs as potential non-invasive biomarkers for distinguishing no-or-mild fibrosis from significant fibrosis in patients with chronic hepatitis B (CHB).

METHODS

Next-generation sequencing was used to identify fibrosis-related serum exosomal miRNAs in 9 CHB patients. The candidate exosomal miRNAs were further validated by qRT-PCR in 282 CHB patients. Receiver operating characteristic curves were generated to assess the diagnostic performance of exosomal miRNAs and other non-invasive models.

RESULTS

Seventy-two miRNAs were differentially expressed in serum exosomes between patients with no-or-mild fibrosis and significant fibrosis. The expression of serum exosomal miR-92a-3p and miR-146a-5p progressively increased with the aggravation of liver fibrosis in the validation cohort. Multivariate analysis identified miR-92a-3p (P<0.001), miR-146a-5p (P<0.001), and liver stiffness measurement (LSM) (P=0.012) as independent predictors for significant fibrosis. The area under the receiver operating characteristic curve (AUROC) of exosomal miR-92a-3p (AUROC=0.88) was significantly higher than that of APRI (aspartate aminotransferase-to-platelet ratio index) (AUROC=0.72, P<0.001), FIB-4 (AUROC=0.71, P<0.001), and LSM (AUROC=0.80, P=0.022) for identifying significant fibrosis. Similarly, the AUROC of exosomal miR-146a-5p (AUROC=0.82) was also significantly better than that of APRI (AUROC=0.72, P=0.009), FIB-4 (AUROC=0.71, P=0.002), and comparable to LSM (AUROC=0.80, P=0.551) for discriminating significant fibrosis.

CONCLUSION

Serum exosomal miR-92a-3p and miR-146a-5p are superior to APRI, FIB-4, and LSM for diagnosing significant fibrosis in CHB patients and offer a promising non-invasive alternative to liver biopsy.